Clinical PET Imaging in Prostate Cancer

Wallitt, Kathryn; Khan, Saba; Dubash, Suraiya; Tam, Henry; Khan, Sameer; Barwick, Tara

doi:10.1148/rg.2017170035

Cited by 102 publications

(80 citation statements)

References 109 publications

(207 reference statements)

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“…With respect to tumor imaging, most of the subjects exhibited an overall radiologic response of the stable disease. One of the reasons for this modest response could be the limitations associated with conventional imaging in staging, restaging after biochemical relapse, and response assessment …”

Section: Discussionmentioning

confidence: 99%

“…for this modest response could be the limitations associated with conventional imaging in staging, restaging after biochemical relapse, and response assessment. 29 Shortly after the initiation of this study, the dose of PSMA ADC was reduced from 2.5 to 2.3 mg/kg due to dose-limiting toxicities (eg, neutropenia and sepsis), which were occurring during the first 3 weeks of treatment (cycle 1). These toxicities have also been reported with other ADCs utilizing MMAE, such as brentuximab vedotin and glembatumumab vedotin.…”

Section: Discussionmentioning

confidence: 99%

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PSMA ADC monotherapy in patients with progressive metastatic castration‐resistant prostate cancer following abiraterone and/or enzalutamide: Efficacy and safety in open‐label single‐arm phase 2 study

et al. 2019

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Background Prostate‐specific membrane antigen (PSMA) is a well‐established therapeutic and diagnostic target overexpressed in both primary and metastatic prostate cancers. PSMA antibody‐drug conjugate (PSMA ADC) is a fully human immunoglobulin G1 anti‐PSMA monoclonal antibody conjugated to monomethylauristatin E, which binds to PSMA‐positive cells and induces cytotoxicity. In a phase 1 study, PSMA ADC was well tolerated and demonstrated activity as measured by reductions in serum prostate‐specific antigen (PSA) and circulating tumor cells (CTCs). To further assess PSMA ADC, we conducted a phase 2 trial in metastatic castration‐resistant prostate cancer (mCRPC) subjects who progressed following abiraterone/enzalutamide (abi/enz) therapy. Methods A total of 119 (84 chemotherapy‐experienced and 35 chemotherapy‐naïve) subjects were administered PSMA ADC 2.5 or 2.3 mg/kg IV q3w for up to eight cycles. Antitumor activity (best percentage declines in PSA and CTCs from baseline and tumor responses through radiological imaging), exploratory biomarkers, and safety (monitoring of adverse events [AEs], clinical laboratory tests, and Eastern Cooperative Oncology Group performance status) were assessed. Results PSA declines ≥50% occurred in 14% of all treated (n = 113) and 21% of chemotherapy‐naïve subjects (n = 34). CTC declines ≥50% were seen in 78% of all treated (n = 77; number of subjects with ≥5 CTCs at baseline and a posttreatment result) and 89% of chemotherapy‐naïve subjects (n = 19); 47% of all treated and 53% of chemotherapy‐naïve subjects had a transition from ≥5 to less than 5 CTCs/7.5 mL blood at some point during the study. PSA and CTC reductions were associated with high PSMA expression (CTCs or tumor tissue) and low neuroendocrine serum markers. In the chemotherapy‐experienced group, the best overall radiologic response to PSMA ADC treatment was stable disease in 51 (60.7%) subjects; 5.7% of subjects in the chemotherapy‐naïve group had partial responses. The most common treatment‐related AEs ≥Common Terminology Criteria for AE (CTCAE) grade 3 were neutropenia, fatigue, electrolyte imbalance, anemia, and neuropathy. The most common serious AEs were dehydration, hyponatremia, febrile neutropenia, and constipation. Two subjects who received 2.5 mg/kg died of sepsis. Conclusions PSMA ADC demonstrated some activity with respect to PSA declines, CTC conversions/reductions, and radiologic assessments in abi/enz treated mCRPC subjects. Clinically significant treatment‐related AEs included neutropenia and neuropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PSMA ADC monotherapy in patients with progressive metastatic castration‐resistant prostate cancer following abiraterone and/or enzalutamide: Efficacy and safety in open‐label single‐arm phase 2 study

et al. 2019

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“…The most widely utilized radiotracer in cancer imaging is F-18-labeled fluoro-2-deoxyglucose (F-18-FDG) in conjunction with PET/CT [12]. The typical appearance of a liposarcoma on F-18-FDG PET/CT varies based upon its internal components and degree of heterogeneity, however, a study by Rahkeja et al demonstrated that a greater degree of radiotracer uptake (established by higher maximum standard uptake values [SUV max ]) correlated with mitotic count and tumor necrosis within a liposarcoma [13].…”

Section: Imaging Appearancementioning

confidence: 99%

“…An additional PET radiotracer typically utilized for biochemical prostate cancer recurrence is the amino acid analogue F-18-fluciclovine, whose mechanism capitalizes on the increased transport and metabolism of amino acids within cancer cells [12]. The uptake of the radiotracer F-18-fluciclovine, however, is nonspecific for prostate cancer and can be seen in benign entities like prostatic hyperplasia though is thought to be advantageous for local prostate cancer recurrence following prostatectomy given its low accumulation of radiotracer within the bladder [12,14]. Additional cases of F-18-fluciclovine's nonspecific uptake have been described in several other entities such as pituitary adenomas, meningiomas, and malignancies such as breast cancer [12,14].…”

Section: Imaging Appearancementioning

confidence: 99%

Incidental dedifferentiated mediastinal liposarcoma on F-18-fluciclovine PET/CT

et al. 2020

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“…Reviews detailing the importance and discovery of new molecular biomarkers 8 for prognosis and the currently used diagnostics and therapeutics 9,10 for PCa have been published. In 2018, refined advances in prostate-specific membrane antigen (PSMA)targeted PET/CT imaging techniques [11][12][13][14][15] using various positron emission radioisotopes for early detection of PCa, management of metastatic castration-resistant prostate cancer (mCRPC), and their applications in detection of recurrent disease by guided biopsy and surgery 16 were published. There are also recent reports that exclusively cover clinical translation of PSMA-targeted 68 Ga and 177 Lu radioisotopes for detection and therapy of PCa in humans.…”

mentioning

confidence: 99%

Comparison of prostate‐specific membrane antigen ligands in clinical translation research for diagnosis of prostate cancer

et al. 2019

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Background Prostate‐specific membrane antigen (PSMA), overexpressed on prostate cancer (PCa), is a well‐characterized cell surface protein to selectively diagnose PCa. PSMA's unique characteristics and its 1000‐fold higher expression in PCa compared with other tissues renders it as a suitable biomarker for detection of PCa in its early stage. In this report, we critically analyze and recommend the requirements needed for the development of variety of PSMA‐targeted molecular imaging agents based on antibodies, small molecule ligands, peptides, and aptamers. The targeting moieties are either conjugated to radionuclear isotopes or near‐infrared agents for efficient diagnosis of PCa. Recent findings From the analysis, it was found that several small molecule–derived PCa imaging agents are approved for clinical trials in Europe and the United States, and few are already in the clinical use for diagnosis of PCa. Even though 111In‐labeled capromab pendetide was approved by the Food and Drug Administration (FDA) and other engineered antibodies are available for detection of PCa, but high production cost, low shelf life (less than 1 month at 4°C), possibility of human immuno reactions, and low blood clearance rate necessitated a need for developing new imaging agents, which are serum stable, cost‐effective, and possesses longer shelf life (6 months), have fast clearance rate from nontargeted tissues during the diagnosis process. It is found that small molecule ligand‐derived imaging agents possesses most of the desired properties expected for an ideal diagnostic agent when compared with other targeting moieties. Conclusion This report discusses in detail the homing moieties used in the development of targeted diagnostic tools for detection of PCa. The merits and demerits of monoclonal antibodies, small molecule ligands, peptides, and aptamers for imaging of PCa and intraoperative guided surgery are extensively analyzed. Among all, urea‐based ligands were found to be most successful in preclinical and clinical trials and show a major promise for future commercialization.

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Clinical PET Imaging in Prostate Cancer

Cited by 102 publications

References 109 publications

PSMA ADC monotherapy in patients with progressive metastatic castration‐resistant prostate cancer following abiraterone and/or enzalutamide: Efficacy and safety in open‐label single‐arm phase 2 study

PSMA ADC monotherapy in patients with progressive metastatic castration‐resistant prostate cancer following abiraterone and/or enzalutamide: Efficacy and safety in open‐label single‐arm phase 2 study

Incidental dedifferentiated mediastinal liposarcoma on F-18-fluciclovine PET/CT

Comparison of prostate‐specific membrane antigen ligands in clinical translation research for diagnosis of prostate cancer

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